EFFECT OF TOTAL PARATHYROIDECTOMY WITHOUT AUTOIMPLANTATION ON PARATHYROID HORMONE LEVEL IN HEMODIALYSIS PATIENTS WITH SECONDARY HYPERPARATHYROIDISM

EFFECT OF TOTAL PARATHYROIDECTOMY WITHOUT AUTOIMPLANTATION ON PARATHYROID HORMONE LEVEL IN HEMODIALYSIS PATIENTS WITH SECONDARY HYPERPARATHYROIDISM

By

Ezzat Abdel-Rahman Eletreby, Waleed Ahmed Massoud

and Hany Abd EL-Ghany Mohamed

Department of Internal Medicine, Al-Azhar Faculty of Medicine

ABSTRACT

Background: Secondary hyperparathyroidism is a major problem in chronic kidney disease patients, resulting in skeletal complications including enhanced osteoclast activity with accelerated bone turnover and osteitis fibrosa cystica.

Objective: Studying the effect of total parathyroidectomy without autoimplantation on PTH level, and state of parathormone activity in hemodialysis patients.

Patients and Methods: Thirty four hemodialysis patients with secondary hyperparathyroidism were subjected for follow up as regard calcium, phosphorus, parathormone (PTH) level, post total parathyroidec-tomy without auto implantation between July 2013 and December 2015 after failure of medical treatment.

Results: The studied patients had a mean age of 52.3 ±5.6 years. They were 15 males (44.1 %) and 19 females (55.8%). Mean of hemodialysis duration was 12.4 ±3.8 years.There was a significant decline of the postoperative parathyroid hormone levels when compared with their preoperative assessments. After 6 months 67.6 % had PTH levels of 3-8 folds more than upper normal of assay, while 5.9% had PTH level below 100 pg-ml, and 26.5 % have PTH level more than 8 folds the upper normal of assay,and symptoms of recurrent hyperparathyroidism.

Conclusion: Total parathyroidectomy without autoimplantation was associated with a low rate of hypopara-thyroism in hemodialysis patients.

Keywords: Parathyroidectomy, hyperparathyroidism, hemodialysis.

INTRODUCTION

     Secondary hyperparathyroidism is a major problem in chronic kidney disease patients resulting in skeletal complications including enhanced osteoclast activity with accelerated bone turnover and osteitis fibrosa cystica (Bureo et al., 2015).

     Medical treatment of secondary hyperparathyroidism consists of active vitamin D2, D3 analogues as alfa calcidol and calcitriol. This treatment is limited by hypercalcemia and aggravation of hyperphosphatemia (Rodriguez and Rodriguez-Ortiz, 2015).

    Surgical treatment is reserved for patients whose PTH values persist above 800 pg/ ml with hyperphosphatemia and hypercalcemia despite medical treatment. Three surgical approaches for parathyroi-dectomy have been reported,i.e. subtotal parathyroidectomy, total parathyroidec-tomy with auto implantation of parathyroid tissue into the forearm musculature and total parathyroidectomy without auto implantation (Lorenz et al., 2015).

    Subtotal or total parathyroidectomy with autoimplantation are done but both are associated with a high recurrence rate.The third surgical strategy is total parathyroidectomy without autoimplanta-tion. Most centers perform either subtotal or total parathyroidectomy with autoimplantation to avoid a possible hypoparathyroidism and the need for calcium and vitamin D supplementation. Recurrence of hyperparathyroidism varies from 5 to 80% in different studies for the first two surgical approaches (Schneider and Bartsch, 2015).

    The present work aimed to study the effect of total parathyroidectomy without autoimplantation on parathyroid hormone level in hemodialysis patients with secondary hyperparathyroidism.

PATIENTS AND METHODS

     The study included 34 patients who were subjected to total parathyroidectomy after consents from the patients.

Inclusion criteria: All hemodialysis patients with secondary hyperparathyroi-dism above 800 pg / ml after failure of medical treatment for at least 6 months. The duration of dialysis for 18 patients were subjected to the study was 7 years, and 16 patients stayed on dialysis for 9 years. The medical treatment given consisted of alphacalcidole 3 microgm (3 times per week), and  calcium based phosphorus binder in form of calcium acetate (700 mg tablet 3 tablets with each meal for 6 months).

    Failure of medical treatment was denoted by occurrence of hypercalcemia, increased calcium phosphorus product and failure of PTH levels to decrease after this treatment.

Stastistical analysis: Data obtained from the present study were computed using SPSS versions 17 under the platform of Microsoft Windows 7. Continuous data were expressed in the form of mean ± SD, while categorical data were expressed in the form of count and percent. Tests used were  ANOVA, Mann Whitney U test,  and using post hoc test with ANOVA test for comparison between groups of data. P value less than 0.05 was considered statistically significant.

RESULTS

      After 6 months of follow up, calcium level was much lower than preoperative calcium (Ca) level (9.2 ± 0.1 vs 7.8 ± 0.8 after 3 months and 8.5 ± 0.7 after 6 months respectively ( Fig.1) and serum phosphorus (P) level was much lower level than preoperative serum phosphorus level (7.3 ± 1.8 vs 4.5 ± 1.0 after 3 months,and 4.7 ± 1.0 at 6 months respectively Fig. 1).

Figure (1): Mean ±SD of Ca and P levels in the studied patients (mg/dl).

Table (1): Mean and SD of Ca, P levels, Ca x P and ALP.

     After 6 months follow up calcium level was much lower than preoperative level 5.8 ± 0.7 and 9.2 ± 0.1 respectively (Fig. 1 and Table 1).

     After 6 months follow up  serum phosphorus level was much lower level than preoperative serum phosphorus level (7.3 ± 1.8 vs 4.5 ± 1.0 at 3 months and 4.7 ± 1.0 at 6 months) (Fig. 1and Table 1).

     The  calcium ´ phosphorus (Ca ´ P) product at 6 months follow up revealed a significant decline in comparison of the  preoperative assessments (67.5 ± 19.6 vs 35.0 ± 7.9 at 3 months and 40.3 ± 10.2 at 6 months (Table 1).

     There  was a significant decline of the postoperative Alkaline phosphatase (ALP) levels when compared with their preoperative assessments (554.8 ± 242.3 vs 346.4 ± 123.5 at 3 months and 241.0 ± 72.8 at 6 months respectively - Table 2).

     There was a significant decline of the postoperative parathyroid hormone (PTH) levels when compared with their preoperative assessments (1195.5 ± 469.4 vs 130.9 ± 70.9 respectively, Table 3).

Table (2): Mean ± SD of  ALP levels in the studied patients (u/L).

Table (3): Mean ± SD of  PTH levels in the studied patients (pg-ml).

    After  6 months postoperative follow up,  23 patients (67.6 %) had  PTH levels  up to 3-8 fold the normal value, while 2 patients (5.8 %) had hypoparathyroidism less than 100 pg/ml and 9 patients (26.47 %) had recurrent hyperparathyroidism  PTH level more than 8 fold of upper normal value  (Table 4 ).  The explanation for occurrence of recurrent hyperpara-thyroidism is the presence of super-numerary  parathyhroid glands which  range from 2.5 to 30% (Schneider et al., 2011), these glands subjected for uremic stimulation and so secondary hyper-parathyroidism  in spite  of doing total parathyroidectomy without autoimplanta-tion.

Table (4): Postoperative PTH outcome.

DISCUSSION

     The relationship between chronic renal insufficiency and secondary hyper-parathyroidism is well established (Pitt et al., 2009).

     Parathyroidectomy to treat secondary hyperparathyroidism is indicated in 15%-38% of chronic renal failure patients over 10-20 years, and has been shown to improve survival for dialysis-dependent patients as well as symptomatology and quality of life (Schneider et al., 2012).

     Hypoparathyroidism after total para-thyroidectomy seems to be rare. in the literature,the presence of supernumerary and ectopic parathyroid glands is quite variable ranging from 2.5 to 30% (Schneider et al., 2011).

     The present study aimed to determine the influence of total parathyroidectomy without autotransplantation on the state of parathyroid activity in patients with chronic renal failure under maintenance hemodialysis.

     Comparison between preoperative and follow up calcium levels showed a significant decline of the postoperative calcium levels at 6 months when compared with their preoperative assessments. These findings were in agreement with the study of Puccini et al. (2010) who reported clinical and laboratory long-term follow-up for total parathyroidectomy without autotransplan-tation for the treatment of secondary hyperparathyroidism associated with chronic kidney disease. The study found significant reduction in Ca, P and ALP levels in the studied patients in the follow up period when compared with controls.

    Our study also found a statistically significant differences between preopera-tive and postoperative PTH levels in the studied patients.  There was a complete improvement of the reported symptoms including  bone  pain, fatigue and pruritis after performing the operation.

    After 6 months postoperative follow up, 67.6 % had the recommended PTH levels 3-8 folds  more  than upper level of assay, while  5.9 %  had PTH level below 100 pg/ml, and 26.5 % had PTH level more than 8 folds  of normal assay. These data seemed better than the study of Coulston et al. (2010). In this study high percentage 28.7% had PTH level below 100pg/ml while in our study, only 5.9% had PTH level less than 100pg/ml.

     In our study 26.5% of patients had recurrent hyperparathyroidism. This finding was in agreement with the study of Thomas and Jacob (2016). In this study, 20% of the patients demonstrated persistent hyperparathyroidism.

CONCLUSION

    There was a low rate of hypoparathyroi-dism and recurrent hyperparathyroidism with total parathyroideetomy without autoimplantation. Total parathyroidec-tomy without autoimplantation was associated with low rate of hypopara-thyroidism and recurrent hyperparathyroi-dism so it is a better option than  the other two surgical modalities.

REFERENCES

1. Bureo JC, Arevalo JC, Anton J, Adrados G, Jimenez Morales J and Robles NR. (2015): Prevalence of secondary hyperparathyroidism in patients with stage 3 and 4 chronic kidney disease seen in internal medicine. Endocrinol Nutr., 62(7): 300-305

2. Coulston JE, Egan R, Willis E and Morgan JD. (2010): Total parathyroidectomy without autotransplantation for renal hyperparathyroi-dism. Br J Surg., 97: 1674-9.

3. Lorenz K, Bartsch DK, Sancho JJ, Guigard S and Triponez F. (2015): Surgical management of secondary hyperparathyroidism in chronic kidney disease-a consensus report of the European Society of Endocrine Surgeons. Langenbecks Arch Surg., 400: 907-927.

4. Pitt SC, Sippel RS and Chen H. (2009): Secondary and tertiary hyperparathyroidism, state of the art surgical management. Surg Clin North America, 89: 1227-39.

5. Puccini M, Carpi A, Cupisti A, Caprioli R, Iacconi P, Barsotti M, Buccianti P, Mechanick J, Nicolini A and Miccoli P. (2010): Total parathyroidectomy without autotransplantation for the treatment of secondary hyperparathyroidism associated with chronic kidney disease: clinical and laboratory long-term follow-up. Biomed Pharmacother., 64(5): 359-62.

6. Rodriguez M and Rodriguez-Ortiz ME. (2015): Advances in pharmacotherapy for secondary hyperparathyroidism.Expert Opin Pharmacother., 16( 11): 1703-16.

7. Schneider R and Bartsch DK. (2015): Role of surgery in the treatment of renal secondary hyperparathyroidism. Br J Surg., 102(4): 289-90.

8. Schneider R, Slater EP, Karakas E, Bartsch DK and Schlosser K. (2012): Initial parathyroid surgery in 606 patients with renal hyperparathyroidism. World J Surg., 36: 318-26.

9. Schneider R,Waldmann J,Ramaswmy A,Fernandez ED,Bartsch DK and Schlosser K. (2011): Frequency of ectopic and super-numerary intrathymic parathyroid glands in patient with renal hyperparathyroidism,World J surg., 35: 1260-5.

10. Thomas H and Jacob A. (2016): Total parathyroidectomy in patients with chronic kidney disease. Saudi J of Kidney Diseases and Transplantation, 27: 950-957.